This proposal examines the mechanisms responsible for pulmonary edema- induced increases in airway responsiveness. Models of both "cardiogenic" and "non-cardiogenic" pulmonary edema will be employed in chronically instrumented awake sheep. "Cardiogenic" pulmonary edema will be induced by increasing left atrial pressure (PLA). "Non-cardiogenic" pulmonary edema will be induced either with Perilla ketone or with endotoxin. Our Specific Aims are to address the following questions: 1) Does non-cardiogenic pulmonary edema increase airway responsiveness more than cardiogenic pulmonary edema? 2) Does the increase in airway responsiveness associated with pulmonary edema correlate with: A) the severity of the pulmonary edema? B) the location of the pulmonary edema? 3) Does the increased airway responsiveness associated with PLA result from: A) prolonged transit time of blood in the bronchial circulation? B) increased hydrostatic pressure? 4) Will cardiogenic pulmonary edema sustained over long periods of time cause: A) greater increases in airway responsiveness? B) more persistent increases in airway responsiveness once PLA is returned to normal? 5) Does the increase in airway responsiveness associated with pulmonary edema require an intact bronchial circulation? 6) Will atropine or vagal blockade attenuate pulmonary edema-induced increases in airway responsiveness? 7) Does pulmonary edema increase airway responsiveness to both aerosol and intravenously delivered bronchoconstrictors? It is probable that we will be able to define a relatively simple relationship between the severity of pulmonary edema and alterations in airway responsiveness. An understanding of the relationship between edema and airway responsiveness should help in the development of a rational approach to the treatment of the altered lung mechanics observed in congestive heart failure, cardiogenic pulmonary edema, and in acute lung injury.